Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

Autor:	Siciliano MC; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Bertolazzi G; Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.; Department of Economics, Business, and Statistics, University of Palermo, Palermo, Italy., Morello G; Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy., Tornambè S; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Del Corvo M; Istituto Europeo di Oncologia (IEO), IRCSS Milano, Milan, Italy., Granai M; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Sapienza MR; Istituto Europeo di Oncologia (IEO), IRCSS Milano, Milan, Italy., Leahy CI; School of Medicine, Bernal Institute, Health Research Institute and Limerick Digital Cancer Research Centre, University of Limerick, Limerick, Ireland., Fennell E; School of Medicine, Bernal Institute, Health Research Institute and Limerick Digital Cancer Research Centre, University of Limerick, Limerick, Ireland., Belmonte B; Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy., Arcuri F; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Vannucchi M; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Mancini V; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Guazzo R; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Boccacci R; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Onyango N; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya., Nyagol J; Department of Human Pathology, University of Nairobi, Nairobi, Kenya., Santi R; Department of Pathology, University of Florence, Florence, Italy., Di Stefano G; Department of Pathology, University of Florence, Florence, Italy., Ferrara D; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Bellan C; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Marafioti T; Department of Cellular Pathology, University College London, London, United Kingdom., Ott G; AbteilungfürKlinischePathologie, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch InstitutfürKlinischePharmakologie, Stuttgart, Germany., Siebert R; Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany., Quintanilla-Fend L; Institut für Pathologie und Neuropathologie, University of Tubingen, Tubingen, Germany., Fend F; Institut für Pathologie und Neuropathologie, University of Tubingen, Tubingen, Germany., Murray P; School of Medicine, Bernal Institute, Health Research Institute and Limerick Digital Cancer Research Centre, University of Limerick, Limerick, Ireland., Tripodo C; School of Medicine, Bernal Institute, Health Research Institute and Limerick Digital Cancer Research Centre, University of Limerick, Limerick, Ireland.; Tumor and Microenvironment Histopathology Unit, IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Pileri S; Istituto Europeo di Oncologia (IEO), IRCSS Milano, Milan, Italy., Lazzi S; Department of Medical Biotechnologies, University of Siena, Siena, Italy., Leoncini L; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Aug 27; Vol. 8 (16), pp. 4330-4343.
DOI:	10.1182/bloodadvances.2023011506
Abstrakt:	Abstract: Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated using multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (cluster 2), EBV- BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky," both EBV+ and EBV-. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, whereas BLs with "starry sky" were characterized by upregulation of M2 polarization and protumor response. Moreover, the analysis of additional signatures revealed an upregulation of the dark zone signature and epigenetic signature in BL with a typical starry sky. Tumor-associated macrophages and epigenetic regulators may be promising targets for additional therapies for BL lymphoma, opening novel immunotherapeutic strategies. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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